Cyclic Adenosine 3′,5′-Monophosphate Response Element-Binding Protein and CCAAT/Enhancer-Binding Protein Mediate Prostaglandin E2-Induced Steroidogenic Acute Regulatory Protein Expression in Endometriotic Stromal Cells
Open accessAbstract
Aberrant expression of the steroidogenic acute regulatory (StAR) protein in human endometriotic stromal cells plays an important role in the development of endometriosis. Prostaglandin E(2) (PGE(2)) is a potent inducer of StAR expression in these cells; however, the mechanisms responsible for the transcriptional regulation of StAR remain to be elucidated. Herein we report that PGE(2)-induced StAR expression is independent of the transcriptional suppressor DAX-1 but is regulated by the transcriptional activator cyclic adenosine 3',5'-monophosphate (cAMP) response element-binding protein (CREB). A promoter activity assay revealed that the cis-element needed for the binding of the CCAAT/enhancer-binding protein (C/EBP) was critical for PGE(2)-induced StAR expression. Electrophoretic mobility shift assay demonstrated that this region of the StAR promoter was bound by C/EBPalpha, C/EBPbeta, and CREB. Forced expression of either C/EBPalpha or C/EBPbeta alone was sufficient to up-regulate StAR promoter activity whereas PGE(2) was needed to induce StAR promoter activity in CREB-overexpressed cells. Results from a chromatin immunoprecipitation assay demonstrated that the binding of C/EBPbeta to the StAR promoter was increased whereas CREB binding was unchanged after PGE(2) treatment. Taken together, PGE(2)-induced StAR promoter activity appears to be regulated by CREB and C/EBPbeta in a cooperative manner in ectopic human endometriotic stromal cells, providing a molecular framework for the etiology of endometriosis.
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PGE2 activates PKA signaling via raising intracellular cAMP, which can enhance binding of SF-1 to promoters of steroidogenic genes and induce phosphorylation of CREB.
“PGE2 activates the protein kinase A (PKA) signaling pathway via raising the intracellular levels of cyclic adenosine 3′,5′-monophosphate (cAMP)12–14, which can enhance the binding of steroidogenic factor-1 (SF-1) to promoters of these steroidogenic genes15, and induce phosphorylation of the transcriptional activator cAMP-response element-binding protein (CREB)16.”
From Platelets induce increased estrogen production through NF-κB and TGF-β1 signaling pathways in endometriotic stromal cells (2020) · cites this paper as [16]
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- Authors
- Hsu, C.-C., Lu, C.-W., Huang, B.-M., Wu, M.-H., & Tsai, S.-J.
- Affiliations
- National Cheng Kung University (TW)
- Corresponding author
- Tsai, Shaw-Jenq
- Venue
- The American Journal of Pathology
- Publisher
- Elsevier BV
- Published
- 2008-08
- Volume
- 173
- Issue
- 2
- Pages
- 433-441
- ISSN
- 0002-9440 (ISSN-L)
- PMC
- PMC2475780
- OpenAlex
- W1976913846
- Cited by
- 30
- References
- 34
- Citations by year
- 2022: 2 · 2021: 1 · 2020: 3 · 2019: 2 · 2018: 2 · 2017: 2 · 2016: 4 · 2015: 2 · 2014: 2
- FWCI
- 3.86
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- American Journal Of Pathology (publishedVersion)
- Europe PMC (PubMed Central) (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Science Council
- Topics
- Health Sciences › Medicine › Reproductive Medicine › Endometriosis Research and Treatment
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Estrogen and related hormone effects
- Health Sciences › Medicine › Pharmacology › Inflammatory mediators and NSAID effects
- Keywords
- steroidogenic acute regulatory protein, endometriosis, endometriotic stromal cells, prostaglandin E2, CREB, C/EBPβ, C/EBPα, transcriptional regulation, DAX-1, steroidogenesis
- MeSH terms
- Steroidogenic Acute Regulatory Protein, Binding Sites, Cells, Cultured, DNA-Binding Proteins, Endometriosis, Female, Gene Expression Regulation, Humans, Phosphoproteins, Promoter Regions, Genetic, Repressor Proteins, Dinoprostone, Stromal Cells, Cyclic AMP Response Element-Binding Protein, Receptors, Retinoic Acid, Response Elements, CCAAT-Enhancer-Binding Proteins, DAX-1 Orphan Nuclear Receptor
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